HIV-1 vaccines and screening methods therefor

Abstract

Methods for immunizing, and immunogen pharmaceutical compositions for eliciting a heterologous immune response to HIV-1 in an animal, preferably a human, are provided, utilizing a modified HIV-1 envelope protein or fragment or DNA encoding a modified HIV-1 envelope protein or fragment, the modified protein having a HIV-1 envelope protein V2 region deletion. A humoral response against heterologous HIV-1 strains is achieved.

What is claimed is:  
     
         1 . A method for immunizing an animal against heterologous HIV-1 comprising administering to said animal an immunogen comprising at least one modified HIV-1 envelope protein or fragment thereof, or DNA or virus encoding said at least one modified HIV-1 envelope protein or fragment thereof, or a combination thereof, said modified envelope protein or fragment thereof having a V2 region deletion, wherein said animal exhibits immunity to at least one HIV-1 strain other than that of said immunogen.  
     
     
         2 . The method of  claim 1  wherein said immunity comprises a humoral response.  
     
     
         3 . The method of  claim 1  wherein said immunogen comprises a modified HIV-1 envelope protein from a clade-B HIV-1 strain.  
     
     
         4 . The method of  claim 3  wherein said HIV-strain is SF162.  
     
     
         5 . The method of  claim 4  wherein said modified HIV-1 envelope protein is SEQ ID No:2 or SEQ ID No:4.  
     
     
         5 . The method of  claim 4  wherein said DNA encoding said at least one modified HIV-1 envelope protein is SEQ ID No:1 or SEQ ID No:3.  
     
     
         6 . The method of  claim 2  wherein said humoral response comprises neutralizing antibodies.  
     
     
         7 . The method of  claim 2  wherein said humoral response comprises protective antibodies.  
     
     
         8 . The method of  claim 1  wherein said animal is a human.  
     
     
         9 . A method for eliciting a heterologous immune response to HIV-1 in an animal comprising immunizing said animal with an immunogen comprising at least one modified HIV-1 envelope protein or fragment thereof, or DNA or virus encoding said at least one modified HIV-1 envelope protein or fragment thereof, or a combination thereof, said modified envelope protein or fragment thereof having a V2 region deletion, wherein said animal exhibits a an envelope-specific immune response to at least one HIV-1 strain other than that of said immunogen.  
     
     
         10 . The method of  claim 9  wherein said envelope-specific immune response comprises a humoral response.  
     
     
         11 . The method of  claim 9  wherein said immunogen comprises a modified HIV-1 envelope protein from a clade-B HIV-1 strain.  
     
     
         12 . The method of  claim 11  wherein said HIV-strain is SF162.  
     
     
         13 . The method of  claim 12  wherein said modified HIV-1 envelope protein is SEQ ID No:2 or SEQ ID No:4.  
     
     
         14 . The method of  claim 12  wherein said DNA encoding said at least one modified HIV-1 envelope protein is SEQ ID No:1 or SEQ ID No:3.  
     
     
         15 . The method of  claim 10  wherein said humoral response comprises neutralizing antibodies.  
     
     
         16 . The method of  claim 10  wherein said humoral response comprises protective antibodies.  
     
     
         17 . The method of  claim 9  wherein said animal is a human.  
     
     
         18 . A pharmaceutical composition for immunizing an animal against HIV-1 virus comprising an effective heterologous envelope-specific immune response-eliciting amount of at least one modified HIV-1 envelope protein or fragment thereof, or DNA or virus encoding said at least one modified HIV-1 envelope protein or fragment thereof, or a combination thereof, said modified envelope protein or fragment thereof having a V2 region deletion; and a pharmaceutically-acceptable carrier or excipient.  
     
     
         19 . The pharmaceutical composition of  claim 18  wherein said modified HIV-1 envelope protein is from a clade-B HIV-1 strain.  
     
     
         20 . The pharmaceutical composition of  claim 19  wherein said HIV-1 strain is SF162.  
     
     
         21 . The pharmaceutical composition of  claim 20  wherein said modified HIV-1 envelope protein is SEQ ID No:2 or SEQ ID No:4.  
     
     
         22 . The pharmaceutical composition of  claim 20  wherein said DNA encoding said at least one modified HIV-1 envelope protein is SEQ ID No:1 or SEQ ID No:3.  
     
     
         23 . A method for assessing whether a compound is capable of generating protective antibodies in an animal against at least one heterologous strain of HIV-1, said animal capable of developing protective antibodies against wild-type HIV-1, said method comprising the steps of immunizing said animal with said compound, depleting said animal of its CD8+ T-lymphocytes, and assessing the presence of protective antibodies in the said animal to at least one heterologous strain of HIV-1.  
     
     
         24 . The method of  claim 23  wherein said depleting is carried out by administering to said animal anti-CD8 monoclonal antibodies.  
     
     
         25 . The method of  claim 23  wherein said compound is an HIV-derived polypeptide or fragment thereof or a DNA or virus encoding said peptide or fragment thereof.  
     
     
         26 . The method of  claim 23  wherein said immunizing is carried out with a DNA vaccine, a protein, or a combination thereof.  
     
     
         27 . The method of  claim 23  wherein said neutralizing antibodies are protective antibodies.